PGE.sub.1 is a naturally occurring prostaglandin. Further, various salts and lower alkyl esters of PGE.sub.1 are known in the art. See, for example, U.S. Pat. No. 3,069,322. Likewise PGE.sub.1 amide is described at Derwent Farmdoc CPI 32921W, abstracting French Published Application No. 2,239,458.
PGE.sub.1, its lower alkyl esters, salts, and amide are known to be potent pharmacological agents. In particular, PGE.sub.1 is known to be a potent vasodilator.
However, prostaglandins, including PGE.sub.1, are known to be readily, metabolically inactivated, particularly during pulmonary circulation. Ferreira and Vane (Nature 216, 868, 1967) found that the biological activity of prostaglandin E.sub.1 and E.sub.2, although stable in blood, almost completely disappeared in a single pass through the pulmonary circulation of dogs, cats, and rabbits. Biron (Clin. Res. 16, 112, 1968) confirmed that over 80 percent of prostaglandins perfused through the lung were extracted in rabbits, rats, cats, and dogs. McGiff et al., (Nature 223, 742, 1969) found that PGE.sub.1 was removed by the lung exceedingly rapidly and concluded that its activities were restricted essentially to the area between the site of introduction into a vein and the site of pulmonary circulation where prostaglandins are inactivated. Horton and Jones (Brit. J. Pharmacol. 37, 705, 1969), cited the work of Ferreira and Vane (above) which showed that more than 95 percent of the smooth muscle stimulating activity of prostaglandin E.sub.2 in the cat and more than 95 percent of the smooth muscle stimulating activity of PGE.sub.1 in the dog were lost on a single passage through the lung, and obtained losses of peripheral vasodilator activity of prostaglandin E.sub.1 on passage through the lung and liver circulation of the cat and dog which agreed closely with those noted above. Piper, Vane, and Wyllie (Nature 225, 600, 1970) and Piper and Vane (in Prostaglandins, Peptides, and Amines, ed. Mantegazza and Horton, 15, Academic Press, London, 1969) confirmed these findings and concluded that prostaglandin E.sub.1, E.sub.2, and F.sub.2 .alpha. are almost completely inactivated by the pulmonary circulation of the cat, dog, rat, and guinea pig. They further established that these prostaglandins were inactivated at all concentrations studied and concluded that an excess of pulmonary enzyme was available which metabolized essentially 100 percent of the PGE reaching the lung. Similarly Samuelsson (Ann. N.Y. Acad. Sci. 180, 138, 1971), injecting tritium labelled PGE into a vein of one arm and removing blood from the other arm found at least 90 percent of the injected prostaglandin had been metabolized during transit through the human lung in 1.5 min. In double-labelled studies, they were able to show that the human lung removed 97 percent of PGE.sub. 2 in 90 seconds and 99.5-100 percent in 4.5 min. (Hamberg and Samuelsson, J. Biol. Chem. 246, 6713, 1971). Using PGF.sub.2 .alpha. as a substrate, Granstrom (Eur. J. Biochem. 27, 462, 1971) found 97 percent to be removed in 90 seconds and 99.5 percent in 3.5 min. These investigations establish that the prostaglandin E's are converted to 15-keto metabolites within seconds after reaching the lung and that the metabolites are relative inactive.
Thus, heretofore the administration of PGE.sub.1 in the treatment of human peripheral vascular disease was known only by administration of the prostaglandin into an artery leading to one or more affected extremities. Accordingly, this intraarterial administration would allow PGE.sub.1 to exert its therapeutic effect at the site of the diseased vascular beds without first passing through the lung, and thus before being subjected to prostaglandin 15-dehydrogenase, prostaglandin 13-reductase or other known prostaglandin-inactivating enzymes of the lung.
However, intraarterial administration as taught in the prior art, represents an especially inconvenient and substantially more traumatic route of adminstration than other more routinely and conventionally employed parenteral routes (e.g., intravenous). Thus, intraarterial administration requires the continuous supervision by highly skilled medical professionals.
For a complete discussion of the nature of and clinical manifestations of human peripheral vascular disease and the method previously known of its intraarterial treatment with prostaglandins, see South African Patent 74/0149.
Further, the parenteral use of PGE.sub.1 as a pharmacological agent, both for therapeutic and prophylactic purposes, is known in the art. For example, in addition to South African Patent No. 74/0149, numerous references describe the use of intravenous and intraarterial prostaglandins, including PGE.sub.1, for maintaining the patency of the ductus arteriosus in newborn infants suffering from the "blue baby" syndrome. See R. B. Elliott, et al., Lancet, Jan. 18, 1975, pp. 140-142; P. M. Olley, et al., Circulation, 53:728 (1976); and F. Coceani, et al., Can. J. Physiol. Pharmacol 51:220 (1973).